PB2643: EFFICACY OF REDUCED-DOSE EMICIZUMAB IN HEMOPHILIA A WITH INHIBITORS: REAL WORLD EXPERIENCE IN MALAYSIA
Authors: Andy Sing Ong Tang, Ching Tiong Ko, Zuraida Saari, Veena Selvaratnam, Lee Ping Chew, Jameela Sathar
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Malaysia, with a total population of 32.8million, reported prevalence of 3.28 per 100,000 population for hemophilia A(HA). Inhibitors developed in 11.4% of our HA patients. The presence of inhibitory alloantibodies impairs quality of life(QoL). The advent of emicizumab potentially improves the outcome. Aims: We aimed to study the clinical outcome of patients who received emicizumab at a reduced dose due to economical reasons. Methods: This was a case series of nine severe HA patients with inhibitors treated with emicizumab in Malaysia between June 2018 and November 2022. The primary endpoint was a reduction of bleeding events. The secondary endpoints included:(a)number of breakthrough bleeds with emicizumab at a reduced dose; (b)QoL assessed using Haemo-QoL-A questionnaire; and (c)adverse events. Results: The median duration of treatment was 198 weeks(33-233). Seven(77.8%) had achieved zero bleeding events after receiving emicizumab at standard dose. One had an episode of haemarthrosis which fully resolved after emicizumab administration without requiring any bypassing agents. Another had haematuria due to ureteric stone. Six patients, who required walking aids prior to emicizumab, were able to ambulate independently after emicizumab commencement. QoL improvement was seen in all domains(p-value<0.001). In resource-restricted setting(after the end of compassionate programme), emicizumab dose was tapered down. Following dose reduction, five(55.6%) had an episode of bleeding event while receiving emicizumab at a dose below 1.8mg/kg/month. One had knee hemarthrosis at a dose of 2.8mg/kg 3-weekly. QoL assessment showed no statistical difference after dose reduction(Figure 1; p-value 0.109; paired sample t-test). No thromboembolic events were reported. Summary/Conclusion: Emicizumab has a favourable safety profile with encouraging efficacy in HA patients with inhibitors, even at a reduced dose proven for a duration beyond three years. This might not be current standard of care, but due to cost constraints in developing countries, it is worth conducting future studies for validation. Figure 1. Health-related quality of life scores by 6 domains (Haemo-QoL-A) - Before emicizumab (A)* After 24 weeks of emicizumab (B)* Difference (B-A)* p-value+ 24 weeks after emicizumab dose reduction@ (C)* Difference (C-B)* p-value+ Physical functioning 13.09 (±5.83) 80.00 (±9.43) 66.91 (±9.60) <0.001 71.68 (±13.46) -8.32 (±11.90) 0.069 Role functioning 24.44 (±11.23) 83.03 (±12.30) 58.59 (±10.45) <0.001 76.57 (±10.38) -6.46 (±9.36) 0.072 Worry 29.33 (±25.92) 83.11 (±13.82) 53.78 (±21.92) <0.001 74.67 (±18.22) -8.44 (±14.34) 0.115 Consequences of bleeding 16.82 (±10.61) 79.05 (±13.25) 62.23 (±16.13) <0.001 72.36 (±13.80) -6.69 (±11.15) 0.110 Emotional impact 44.08 (±20.11) 85.93 (±14.12) 41.84 (±17.72) <0.001 74.44 (±14.91) -11.49 (±14.92) 0.050 Treatment concern 22.97 (±25.82) 79.26 (±23.20) 56.29 (±26.48) <0.001 82.22 (±11.06) 2.96 (±20.84) 0.681 Overall transformed score 25.12 (±10.55) 81.73 (±9.70) 56.61 (±11.14) <0.001 75.32 (±10.64) -6.41 (±10.68) 0.109 *mean (±SD)+Paired sample t-test@One patient did not have data for 24 weeks post dose reduction Keywords: Hemophilia A